The purpose of this new project is to study the three dimensional structure of both beta-epidermal growth factor (beta-EGF) and transforming growth factor-type 1 (alpha-TGF) and their synthetic analogs to elucidate their biological action. The methods used include synthesis of peptides by the solid phase method, binding assays, nuclear magnetic resonance (NMR) spectroscopy, computer graphic techniques, and x-ray diffraction. The research focuses on the following areas: (1) the solid phase synthesis of the binding region of both beta-EGF and alpha-TGF; (2) cyclization of synthetic peptides to form disulfide linkages between cystein residues by a high dilution method; (3) binding assays to test their biological activities; (4) conformation studies of both synthetic beta-EGF and alpha-TGF by modern two-dimensional NMR techniques; (5) using computer graphic techniques to design possible antagonists of alpha-TGF, and synthesizing peptides for biological testing; (6) using NMR spectroscopy to study the conformation of both beta-EGF and alpha-TGF in order to determine whether the synthetic peptides resemble the natural protein conformations; and (7) x-ray studies of both beta-EGF and alpha-TGF for comparison of their crystal and solution structures. The binding regions of both beta-EGF and alpha-TFF have alrady been successfully synthesized. Cyclization between two cysteins will be carried out soon.